The complement receptor (CR) of B lymphocytes is expressed evidently late during development of the B cell lineage. Functional studies in vivo and in vitro have shown that both CR positive ("late") and CR negative ("early") B lymphocytes are capable of producing antibody. The central question of this proposal is whether CR negative populations can differentiate to plaque forming cells (PFC) without passing through a CR positive differentiative state, or whether the CR positive state is an obligatory intermediary. Since the in vitro immune response requires the complex interaction of several cell types (which may obscure the issue of B cell differentiation), we propose to use LPS for polyclonal activation of B cells in the absence of accessory cells. We will determine the kinetics of initiation of Ig synthesis in isolated CR negative and CR positive B cell populations. Starting with CR negative B cells, we will induce CR by culturing with LPS, and test whether after removal of CR positive cells Ig synthesis is delayed. Based on our observation that factors derived from helper T cells induce differentiation in early B cells, we will investigate the significance of an intact T cell compartment for the maturation of B cells. We will analyze the state of B cell maturity in T cell deficient mice and attempt to reconstitute the T cell compartment if defects in the B cell lineage become apparent.